Breast cancer is the most common cancer among women in developed countries. In the United States, there were approximately 180,000 new cases expected in 1997, accounting for 30% of all new cancer cases among women. Currently understood breast cancer risk factors account for only about half of breast cancer risk. We propose to investigate the role of gene-environment interactions in breast cancer risk by enrolling and following a cohort of 50,000 sisters of breast cancer cases. Such sisters are at increased risk for breast cancer, giving us enhanced statistical power to detect interactions. The cohort would be large enough to have sufficient cases for examination of many gene- environment interactions after 5 years, but could also be followed longer to create a larger resource for future use. We estimate that a cohort of 50,000 sisters aged 30-74 years would provide about 1,500 breast cancer cases over 5 years. A nationwide campaign will be initiated to recruit sisters. Several recruitment strategies will be pilot-tested before full-scale initiation of the study. Proposed strategies would focus on intensive publicity campaigns but would also take advantage of the large networks of breast cancer advocates. At enrollment we would screen women for eligibility and obtain self- administered questionnaire data as well as a blood sample to be frozen for later use. Other biological specimens such as urine or hair might also be collected. Women with interesting environmental or occupational exposures would be telephoned to complete more detailed exposure interviews. The cohort would be followed actively over time for the development of breast cancer and other diseases. Tumor tissue and medical records will be sought for incident breast cancer cases. Nested case-control or case-cohort analyses will be carried out among sisters who develop cancer and a sample of those who dont, to assess specific gene-environment interactions. Once assembled, the cohort also will provide the structure for assessing gene-environment interactions in risk for other diseases and will provide opportunities for add-on studies such as comparing tumor characteristics and risk factors in affected sister-pairs. - breast cancer cohorts familial epidemiology risk factors genetics sisters - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only